Alpha hydroxy acids (AHA) are a class of organic chemical compounds that contain at least one hydroxyl group and at least one carboxyl group, and wherein the hydroxyl group is located on the alpha carbon atom. Included within the AHAs are lactic acid, glycolic acid, citric acid, malic acid, and tartaric acid. Lactic acid and glycolic acid are the AHAs that are most commonly present in topically applied dermatologic formulations. Other AHAs include tartronic acid, glucuronic acid, pyruvic acid, 2-hydroxyisobutyric acid, 3-hydroxybutyric acid, galacturonic acid, mandelic acid, mucic α-phenyllactic acid, α-phenylpyruvic acid, saccharic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, α-hydroxyisocaproic acid, α-hydroxyisovaleric acid, atrolactic acid, galactanic acid, pantoic acid, glyceric acid, isocitric acid, dihydroxymaleic acid, dihydroxytartaric acid, dihydroxy-fumaric acid and benzylformic acid.
Formulations containing an alpha hydroxy acid (AHA) have long been used by dermatologists and other skin-care professionals in the treatment of certain skin disorders, such as dry skin, including xerosis and ichthyoses. AHAs have been shown to have beneficial moisturizing, keratolytic, and exfoliant effects. There is also evidence that AHAs stimulate collagen and elastin production and are reported to improve wrinkling, roughness, and mottled pigmentation of skin.
One problem with presently available formulations of AHA is that they often cause irritation to skin. The irritation due to the AHA is primarily due to the presence of the AHA itself and of the low pH of these formulations. For example, glycolic acid has a pKa of 3.8. Therefore, in a formulation at this pH, 50% of the glycolic acid will be ionized and 50% will be non-ionized. At pH lower than the pKa, higher proportions of the AHA will be in the non-ionized form and at pH higher than the pKa, higher proportions of the AHA will be in the ionized form.
Because the AHAs perform their desirable dermatologic functions better in the non-ionized form, the products are formulated at as low a pH as is practical. The low pH is irritating to skin. Additionally, high concentrations of AHA are directly irritating to skin. In fact, when used in concentrations of 20% or higher that are effective as a chemical peel to remove scars and wrinkles, redness and stinging associated with this type of therapy can endure for several weeks following treatment.
Epstein, U.S. Pat. No. 5,759,558 discloses an emulsion containing an AHA, a quaternary ammonium cationic emulsifier, and petrolatum or mineral oil. The emulsion of Epstein may also contain one or more of a fatty alcohol having a carbon chain length between C12 to C32, in a concentration of 1 to about 8 weight %, a fatty ester emollient at this same concentration range, and a silicone oil at a concentration of 0.1 to 5 weight %.
Hahn, U.S. Pat. No. 5,804,203, discloses compositions containing an AHA. In order to reduce the skin irritation associated with the AHA, the compositions include an aqueous soluble cation of strontium (Sr2+) in a concentration effective to prevent or reduce the skin irritation due to the AHA. The concentration of strontium ion in the composition needed to achieve this anti-irritant effect is 50 mM or more, although this concentration of strontium can be halved if appropriate levels of a calcium channel blocking agent, a sodium channel blocking agent, or a steroidal or non-steroidal anti-inflammatory compound is included in the composition.
Bobier-Rival, U.S. Pat. No. 5,652,266, discloses a composition containing three active ingredients; an AHA, salicylic acid, and a retinoid. As disclosed in Bobier-Rival, the use of these three ingredients in combination permits lower concentrations of an AHA to be used and so reduces the irritating effects of the AHA.
Charlton, U.S. Pat. No. 6,162,774, discloses that the combination of an AHA in a detergent base comprising a mixture of a non-ionic alkylpolyglucoside surfactant and an amphoteric surfactant reduces irritation and enables compositions to be formulated at low pH between 3.0 and 4.5. The invention of Charlton is disclosed to be effective, however, with concentrations of AHA only up to 10%.
Heath, U.S. Pat. No. 5,407,958, discloses a therapeutic composition that contains one or more AHAs and a preservative, sodium hydroxymethylglycinate, which is provided in the composition to neutralize the AHA and reduce skin irritation. The compositions of Heath also contain a silicone, such as cyclomethicone and/or dimethicone, and may contain branched chain hydrocarbons. The pH of the Heath compositions is higher than 5.0.
Merz Pharmaceuticals, LLC (Greensboro, N.C.), markets a line of skin care products containing glycolic acid (Aqua Glycolic®). These products include a facial cleanser containing 12% glycolic acid, a toner containing 11% glycolic acid, a face cream containing 10% glycolic acid, a shampoo & body cleanser containing 14% glycolic acid, and a hand & body lotion containing 14% glycolic acid. Irritation is a problem with these products. With each of these products, a user is instructed to watch for irritation and to use these products only once daily, and to only increase to twice daily if there is no irritation.
Upsher-Smith Laboratories, Inc. (Minneapolis, Minn.) markets a line of skin care products containing 12% lactic acid (AmLactin®). These products are the commercial embodiment of the invention disclosed in Rood, U.S. Patent Publication 2005/0059644. The AmLactin® products contain, in addition to the AHA in its acid form, an ammonium salt of the AHA which raises the pH of these products to between 4.5 and 5.5. Possibly due to the high pH of these products, they have been shown to have very low irritancy potential. One disadvantage of these products and their high pH is that AHAs perform better when the AHA is in a non-ionized form, and the percentage of the non-ionized form relative to the ionized form of the AHA decreases with increasing pH. Therefore, it would be advantageous to provide a non-irritating formulation of an AHA that is at a pH of 4.0 or lower.
A significant need remains for a non-irritating formulation of an AHA, especially one that has a concentration of higher than 10% and which can be used safely multiple times daily.